ABSTRACT
The tunicamycin biosynthetic gene cluster of Streptomyces chartreusis consists of 14 genes (tunA to tunN) with a high degree of apparent translational coupling. Transcriptional analysis revealed that all of these genes are likely to be transcribed as a single operon from two promoters, tunp1 and tunp2. In-frame deletion analysis revealed that just six of these genes (tunABCDEH) are essential for tunicamycin production in the heterologous host Streptomyces coelicolor, while five (tunFGKLN) with likely counterparts in primary metabolism are not necessary, but presumably ensure efficient production of the antibiotic at the onset of tunicamycin biosynthesis. Three genes are implicated in immunity, namely, tunI and tunJ, which encode a two-component ABC transporter presumably required for export of the antibiotic, and tunM, which encodes a putative S-adenosylmethionine (SAM)-dependent methyltransferase. Expression of tunIJ or tunM in S. coelicolor conferred resistance to exogenous tunicamycin. The results presented here provide new insights into tunicamycin biosynthesis and immunity.
FOOTNOTES
- Received 26 January 2018.
- Returned for modification 4 March 2018.
- Accepted 10 May 2018.
- Accepted manuscript posted online 29 May 2018.
Supplemental material for this article may be found at https://doi.org/10.1128/AAC.00130-18.
- Copyright © 2018 Widdick et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
